Few studies have assessed adherence to human immunodeficiency virus (HIV) antiretroviral therapy (ART) for children living in resource-limited countries. Initial reports indicate that it is suboptimal, with as few as 50% of children achieving a high level of adherence. Adherence has been shown to have strong relationships with viral suppression, progression of HIV to the acquired immunodeficiency syndrome, and death in adults, largely in resource-rich settings. In contrast, we understand very little about adherence in children in developing countries. Valid measurement of adherence in children is the necessary first step in understanding the need and direction of interventions required for optimal pediatric HIV treatment outcomes in developing countries. We propose to conduct a first-of-its-kind longitudinal observational study of objectively measured adherence to ART in children aged 5 to 10 years in a resource-poor setting. We will study children receiving ART in response to a Ugandan government-led impetus to scale up the provision of ART and as part of an ongoing collaboration between the University of California San Francisco and Mbarara University of Science and Technology. In this study, we will first validate several candidate measures of adherence to antiretroviral therapy through correlation with each other and HIV RNA levels. These measures include unannounced pill counts and liquid weights, self-report, a medication event monitoring system, and pharmacy dispensing records. Using these candidate measures, we will then determine the distribution of adherence to antiretroviral therapy in HIV-infected children aged 5 to 10 years in Mbarara, Uganda. We will explore the feasibility of a novel adherence measure in which cell phones are used to perform unannounced pill counts and liquid weights in a resource-limited setting. Finally, we will explore the factors influencing a child's adherence to ART in the context of a culturally validated version of the information, motivation and behavioral skills model of adherence behavior to guide subsequent ART antiretroviral adherence interventions in resource-limited settings. An estimated 2.3 million children under the age of15 are living with HIV/AIDS in the world, with nearly 80% living in sub-Saharan Africa. Antiretroviral therapy is becoming available for these children, and valid characterization of antiretroviral adherence is needed for assessing future adherence interventions. The data derived from this study will be essential for improving health outcomes for these children, as well as decreasing the risk for secondary transmission as these children enter adolescence.